Our previous studies have shown that starvation, diabetes, and clofibrate administration increase oxidation of branched-chain amino acids by rat skeletal muscle. This increased oxidation appeared to be chiefly the function of the increased activity of branched-chain keto acid dehydrogenase of the skeletal muscle by ketone bodies. The present studies are planned to investigate the physiological and clinical relevance of these observations in man. Studies are planned to determine the oxidation and turnover of branched-chain amino acids before and during weight reduction in obese patients, before and after insulin therapy in diabetic patients, before and after a week of protein deprivation in human volunteers, before and after steroid therapy, before and after recovery from protein-calorie malnutrition, before and after supplementation of diet with leucine, before and after carnitine therapy in patients with hyperlipidemias, and before and after clofibrate therapy in patients with hyperlipidemias. In the above studies, we also plan to investigate the possibility of relationships among ketogenesis and muscle proteolysis, plasma carnitine levels and oxidation and turnover of branched-chain amino acids in man. In addition to human studies, we have also planned a series of studies in animals. These studies are planned to examine the possibility of nutritional and metabolic regulation of oxidation of the products of branched-chain amino acid alpha-decarboxylation. Currently there is very little known about these aspects of branched-chain amino acid metabolism. In particular, we will focus our attention on the effects of starvation, diabetes and protein deprivation on the activity of enzymes concerned with the oxidation of isovaleryl-CoA, 3-methylcrotonyl-CoA and beta-hydroxy-beta-methylglutaryl-CoA.